Aislinn Antrim, Associate Editor

Nearly 25% of patients taking methotrexate for common immune system disorders exhibit a weaker immune response to COVID-19 vaccines, according to a new study published in 

Scientists have previously established that patients with rheumatoid arthritis who take methotrexate have a reduced response to seasonal flu vaccines. Because mRNA vaccines, such as the COVID-19 vaccine developed by Pfizer and BioNTech, use a new mechanism of action that patients’ bodies have not experienced before, the investigators sought to evaluate how well these patients are protected after vaccination.

According to the study, immune system disorders occur when the immune system is triggered abnormally, causing inflammation as immune cells rush into damaged or infected tissue. These illnesses, called immune-mediated inflammatory disorders, are typically treated with drugs such as methotrexate to reduce inflammation, according to the study.

To investigate patient responses to the Pfizer-BioNTech COVID-19 vaccine, researchers at the New York University Grossman School of Medicine analyzed the antibodies produced in each patient after receiving the vaccine. Once injected into the body, the investigators said vaccine ingredients are meant to trigger the production of antibodies, which then disable the viral target protein and tag it for removal from the body.

Notably, the lower antibody response in patients taking methotrexate does not necessarily mean that these patients are not protected against COVID-19, co-first study author Rebecca Haberman, MD, said in a press release.

“It is most important to state that patients should not be concerned about our study findings, as the majority of patients with immune system disorders are responding well to the mRNA vaccines,” Haberman said. “It is also possible that methotrexate is delaying, rather than preventing, an adequate immune response against COVID-19.”

The study enrolled healthy people and patients receiving treatment for common immune-mediated disorders, including rheumatoid arthritis, psoriatic arthritis, and psoriasis. Participants received 2 doses of the Pfizer-BioNTech mRNA COVID-19 vaccine and the investigators then analyzed blood samples to determine the amount of antibodies produced.

They found that more than 90% of healthy subjects and patients taking drugs other than methotrexate mounted strong antibody responses, whereas only 62% of people with immune-mediated inflammatory disorders who were taking methotrexate achieved an adequate response. Similarly, patients taking methotrexate did not show an increase in CD8 T cell activation after vaccination, unlike healthy patients and those taking anti-inflammatory drugs other than methotrexate.

“More research is needed to understand why such a significant proportion of people with common immune disorders who take methotrexate have deficiencies in mounting an antibody and cellular response,” said co-senior author Jose U. Scher, MD, in the press release. “This may not necessarily mean that the vaccine is not efficacious, but that alternate vaccine strategies need to be investigated.”

These alternatives could include discontinuing methotrexate when patients receive the vaccine, changing the dosage of methotrexate or potentially administering a booster shot. The research team is currently leading studies to determine which of these alternatives would work best.

Patients Taking Methotrexate Respond Less Well to COVID-19 Vaccine. News release. NYU Langone Health; June 2, 2021. Accessed June 10, 2021. 

https://nyulangone.org/news/patients-taking-methotrexate-respond-less-well-covid-19-vaccine

Articles

A lower antibody response found in one-fourth of patients taking methotrexate does not necessarily mean that these patients are not protected against COVID-19.

Study Suggests Some Patients Taking Anti-Inflammatory Drugs May Have Weaker Immune Response to COVID-19 Vaccines

In women with advanced ovarian cancer, a PARP inhibitor used as maintenance therapy after primary treatment has been shown to significantly lengthen progression-free survival (PFS).

The drug, olaparib (Lynparza; AstraZeneca), is an oral targeted chemotherapy drug that stops the cancer cell’s PARP enzyme from repairing DNA damage, which makes it important in disease progression.

An estimated 21,410 new diagnoses of ovarian cancer in the United States are projected for 2021, and about 13,770 women will die from ovarian cancer this year, according to the American Cancer Society.

Used as maintenance therapy for 2 years after primary treatment of women with advanced ovarian cancer, olaparib has been shown to significantly lengthen 5-year PFS, according to results of the SOLO-1 study (NCT01844986).

“Even years after patients completed the planned 2 years of olaparib treatment, their progression-free survival benefit endured,” lead author, William Bradley, MD, a gynecologic oncologist at Froedtert and the Medical College of Wisconsin, Milwaukee, said in a prepared statement. “That’s very good news.”

Data from the SOLO-1 study that investigated olaparib was presented during 2021 sessions at the Hematology/ Oncology Pharmacy Association (HOPA) virtual conference and the Society of Gynecologic Oncology (SGO) Virtual Annual Meeting on Women’s Cancer.

The objective of maintenance therapy is to slow the cancer’s growth after initial treatment, usually with platinum-based chemotherapy and surgical treatment. Olaparib was studied in patients with a mutation, or harmful alteration, of the BRCA1 and/or BRCA2 genes. The mutation is present in about one-fourth of women with ovarian cancer, according to Bradley.

The SOLO-1 study evaluated 5 years of follow-up data from a prior study, which Bradley called “the longest follow-up for any PARP inhibitor in the setting of maintenance therapy after primary therapy” during the SGO session.

Colleen Bohnenkamp, PharmD, BCOP, BCPS, reviewed the traditional treatment pathway during the HOPA presentation. The treatment pathway begins with neoadjuvant platinum-based chemotherapy for eligible patients, followed by surgical staging and debulking, adjuvant platinum-based chemotherapy, observation or frontline maintenance therapy, and more chemotherapy if a relapse occurs, she said. An occurrence within 6 months of chemotherapy, she noted, is considered platinum-resistant and has lower survival rates, whereas an occurrence more than 6 months after chemotherapy is platinum-sensitive.

According to Bohnenkamp, olaparib was the first approved frontline PARP inhibitor, with its approval based on the SOLO-1 trial. Results were first
reported in 2018, with investigators finding a long PFS benefit. Notably, the secondary outcome of a second median PFS has not yet been reached. These findings suggest that olaparib does not limit patients’ ability to respond to future therapies, which Bohnenkamp said is an important consideration without an abundance of clinical data yet.

The SOLO-1 study included 391 patients with a BRCA mutation and newly diagnosed advanced ovarian cancer who first completed platinum-based chemotherapy. Olaparib was given at random to 260 women; 131 others received a placebo for 2 years or until the cancer worsened.

The data analysis found that more than twice as many women who received olaparib were alive 5 years after the beginning of the study with no progression of their cancer. More than 48% of olaparib recipients had 5-year PFS vs only 20.5% of placebo recipients, according to the study authors.

Further, the researchers analyzed subgroups of patients depending on their risk of disease progression; compared with those who got placebo, olaparib recipients had better 5-year PFS regardless of their initial progression risk.

“Olaparib maintenance therapy should be a standard of care for women with a BRCA mutation and advanced ovarian cancer,” Bradley said.

The safety profile of olaparib shown in SOLO-1 was consistent with previous observations, according to the study authors.

 These results shared a consistent safety profile with the SOLO-2 trial (NCT03470805), with anemia and neutropenia noted as common adverse events (AEs).

Potential AEs of olaparib include blood abnormalities. Bradley suggested that patients taking olaparib receive routine physical assessments and laboratory tests under an oncologist’s care.

Pharmacists can play an important role by closely monitoring patients, including conducting follow-ups between provider visits.

For advanced ovarian cancer, olaparib as maintenance drug reduces disease progression, five-year follow-up data show. News release. Society of Gynecologic Oncology. March 20, 2021. Accessed May 17, 2021. https://www.sgo.org/news/maintenance-olaparib-for-patients-with-newly-diagnosed-advanced-ovarian-cancer-and-a-brca-mutation-5-year-follow-up-from-solo1/

Key statistics for ovarian cancer. American Cancer Society. Reviewed January 12, 2021. Accessed May 11, 2021. https://www.cancer.org/cancer/ovarian-cancer/about/key-statistics.html 

Maintenance olaparib for patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation: 5-year follow-up from SOLO-1. Presented at: Society of Gynecologic Oncology 2021 Annual Meeting on Women’s Cancer; March 19-25, 2021; virtual.

Bohnenkamp C. Approaches to maintenance treatment for ovarian cancer: single agent PARP inhibitor or combination? Presented at: Hematology/Oncology Pharmacy Association Virtual conference; April 14, 2021.

Study results demonstrated consistent benefit across higher
and lower-risk patients.

Findings Link Olaparib as Maintenance Drug to Reduced Disease Progression in Advanced Ovarian Cancer

A new report from Informa Pharma Intelligence found that nearly one-quarter of Americans surveyed would choose none of the 3 currently available COVID-19 vaccines, which the report said reflects a recent policy shift from herd immunity to virus manageability.

“The US is heading toward long-term management of COVID-19, but vaccine hesitancy is still a significant threat in terms of full mitigation,” said Karen Currie, MPH, executive director of Citeline at Informa Pharma Intelligence, in a press release. “Transparency, consistency, and accuracy in communication around the vaccines will be essential to turning the tide on the spread of the virus.”

Although the United States has surpassed the milestone of 100 million COVID-19 vaccinations, the report’s authors said reaching 200 million will be significantly more challenging as vaccine hesitancy remains. According to the report, 23% of Americans would not receive either the Johnson & Johnson, Moderna, or Pfizer and BioNTech vaccines based on phase 3 clinical trial results.

Among the 77% of Americans who would choose one of the available vaccines, 42% said they would prefer the vaccine from Pfizer and BioNTech, compared to 25% who preferred Moderna and 9% who preferred Johnson & Johnson.

In surveys from 2020, a major part of this hesitancy came from a lack of understanding about clinical trials, although the researchers noted that levels of understanding have improved since the company’s report released prior to the first COVID-19 vaccine approval. Notably, the percentage of Americans who said they were more likely to take a COVID-19 vaccine if they had more information has dropped from 28% to 14% since 2020.

Furthermore, the number of Americans saying they would be willing to participate in clinical trials nearly doubled from 7% in 2020 to 13% in 2021, which could potentially mean that Americans are more educated on vaccine data. This education stems mainly from public government data, information distributed by vaccine manufacturers, and from conversations with health care providers.

The survey found decreasing levels of distrust, with 18% of respondents indicating they do not trust how quickly the COVID-19 vaccine clinical trials are moving, down from 35% in 2020. Similarly, 16% said they do not believe pharmaceutical companies have consumers’ best interests in mind during clinical trials, compared to 23% in 2020.

Improving vaccine trust and educating patients will be essential to the future of COVID-19 vaccine development, as well. According to the report, Americans noted several clinical trial factors and said they are critical for their willingness to be vaccinated. Specifically, 22% said they would be more likely to take a COVID-19 vaccine if the clinical trials showed sufficient results of working against new variants.

Similarly, 28% of Americans with children under the age of 18 said they were more likely to have their child take a COVID-19 vaccine if they knew pediatric clinical trials showed sufficient safety and efficacy. Finally, 13% said they would be more likely to take a COVID-19 vaccine if they knew the clinical trials were demographically diverse.

“Trust must continue to be built among the American people, government, and pharmaceutical companies as we work together to save lives, effectively corner the virus and emerge from this pandemic,” Currie concluded in the press release.

While Over Three-Quarters of Americans Are Willing to Take at Least One of the Authorized COVID-19 Vaccines, Nearly a Quarter Are Still Hesitant as the US Changes Course on Mitigation Strategy. News release [Email]. Informa Pharma Intelligence. June 3, 2021. Accessed June 8, 2021.

Although the United States has surpassed the milestone of 100 million COVID-19 vaccinations, a study found that reaching 200 million will be significantly more challenging as vaccine hesitancy remains.

Report Finds ‘Uphill Battle’ For Pharmacists Combatting COVID-19 Vaccine Hesitancy

Patients with insulin-treated type 2 diabetes experienced improved blood sugar control and fewer visits to the emergency department (ED) for hypoglycemia when using continuous glucose monitors, according to a new study published in 

Patients with diabetes have traditionally used finger sticks to test their blood sugar levels. Since 2017, however, Medicare has covered the cost of continuous glucose monitors for patients with diabetes who met certain qualifications. The monitor’s sensor transmits blood sugar readings every 5 minutes to a receiver or smartphone, the study noted.

To qualify under Medicare guidelines, a patient generally must give themselves 3 or more shots of insulin daily or use an insulin pump, perform blood glucose testing 4 or more times a day, and consistently communicate with a diabetes care team every 3 to 6 months.

The new retrospective, comparative efficacy study included 5673 patients with type 1 diabetes and 36,080 patients with type 2 diabetes treated with insulin who were self-monitoring their blood glucose. Between January 2015 and December 2019, 3462 patients with type 1 diabetes and 344 with type 2 diabetes began using continuous glucose monitors.

The researchers then evaluated results from before and after the intervention, compared to results among patients who did not use the monitors. The analyses found that continuous glucose monitors were associated with a decline in levels of HbA1c, and also found that the monitors reduced ED visits and hospitalizations for hypoglycemia.

“The improvement in blood sugar control was comparable to what a patient might experience after starting a new diabetes medication,” said lead author Andrew J. Karter, PhD, a senior research scientist with the Kaiser Permanente Northern California Division of Research, in a press release.

Continuous glucose monitors are now considered the standard of care for patients with type 2 diabetes, according to the study. Earlier research has shown that the monitors improve glucose control for patients with type 1 diabetes, as well.

“Selective prescribing of continuous glucose monitors may partially explain the benefits we saw in these patients with type 2 diabetes,” Karter said in the press release. “Doctors appeared to have preferentially prescribed monitors to patients with a history of hypoglycemia or at high risk of hypoglycemia.”

The researchers said the next step is to determine whether there are other patients whose blood sugar would be better controlled with continuous glucose monitors, including patients who may not meet all of the Medicare criteria.

Continuous glucose monitors help manage type 2 diabetes [news release]. Kaiser Permanente; June 2, 2021. Accessed June 10, 2021. 

https://about.kaiserpermanente.org/our-story/health-research/news/continuous-glucose-monitors-help-manage-type-2-diabetes

Continuous glucose monitors were associated with a decline in levels of HbA1c as well as reduced emergency department visits and hospitalizations for hypoglycemia. 